Infection of mice with Leishmania tropica and donovani will be studied, to analyze the mechanisms of acquired immunity in cutaneous and visceral leishmaniasis. Using methods of adoptive immunization it will be determined whether resistance is mediated solely by cellular mechanisms, or requires the synergistic effect of a specific antibody response. Using strains of relatively susceptible and resistant mice, it will be revealed whether the initial fate of Leishmania in the host (determined by native preexisting defenses) has a direct influence on the subsequent development and expression of specific acquired immunity. The basis of the suppression of cell mediated immunity associated with progressive leishmaniasis will be sought. This will involve experiments designed to determine whether suppression represents a decay of existing mediators of protection, or the emergence of immunological suppressor mechanisms. By examining the resolution of a transplanted leishmanial lesion in an immune guinea pig, the relationship between macrophage microbicidal activity and the destruction of the parasite will be determined in vivo. These experiments will employ techniques that directly monitor macrophage microbicidal capacity against the heterologous bacteria Listeria monocytogenes. It is anticipated that these experiments will significantly advance our knowledge of a parasitic disease of major international importance.